Hageman factor becomes activated on contact with certain negatively charged materials. The binding of Hageman factor to one such material, dextran sulphate, will be investigated in a quantitative fashion. A series of dextran sulphates will be prepared by sulphation of dextran. The ability of Hageman factor to bind to these polymers will be investigated using fluorescence titrations and sephadex bead exclusion studies. The number of binding sites per molecule of polymer and the dissociation constants for the binding of Hageman factor will be measured. These data will be correlated with the ability of the polymers to support the activation of Hageman factor. Small monovalent and divalent anions will be tested for binding to Hageman factor using equilibrium ultrafiltration and fluorescence titrations; the number of binding sites per Hageman molecule and the dissociation constants will be determined. The ability of small ions to compete with activating polymeric anions will be investigated using quantitative affinity chromatography on beaded dextran sulphate and spectrophotometric assays of autoactivation. The activation of Hageman factor by sulphatide and the possible activation or binding of Hageman factor by glycosaminoglycans will be studied using the same methods. The long term aims are (1) to provide a quantitative understanding of the contact activation process in normal plasma containing Hageman factor, prekallikrein, factor XI and High Molecular Weight Kininogen; (2) to identify physiological activating surfaces and the manner in which the contact system may operate under conditions of normal homeostasis or during inflammatory reactions.